4.4.7. Project Summary For patients with compromised health (e.g. people with cystic fibrosis (CF) or diabetes), chronic infections are a major challenge. In these patients, minor bacterial infections can persist and form chronic conditions that are non-responsive to antibiotics that kill the pathogen in vitro. The lack of efficacy in vivo is commonly attributed to differences in the physiological state of the bacteria during chronic infection (e.g. slow growth, persister phenotypes, biofilm production); however these physiological states are also themselves evolvable. In this proposal, we aim to understand evolutionary dynamics during Pseudomonas aeruginosa adaptation to chronic CF lung infection. Our overarching hypothesis is that initial P. aeruginosa colonists are poorly adapted to the CF lung infection environment, and adapt by optimizing investment in survival strategies rather than maximizing fecundity. We will test this hypothesis using an array of genomic and modeling techniques with the goal of opening paths towards improved mechanisms of control.